Action potential

It is over 60 years since Hodgkin and
Huxley1 made the first direct recording of
the electrical changes across the neuronal
membrane that mediate the action
potential. Using an electrode placed inside a
squid giant axon they were able to measure a
transmembrane potential of around 260 mV
inside relative to outside, under resting
conditions (this is called the resting membrane
potential). The action potential is a
transient (,1 millisecond) reversal in the
polarity of this transmembrane potential
which then moves from its point of initiation,
down the axon, to the axon terminals. In a
subsequent series of elegant experiments
Hodgkin and Huxley, along with Bernard
Katz, discovered that the action potential
results from transient changes in the permeability
of the axon membrane to sodium (Na+)
and potassium (K+) ions. Importantly, Na+ and
K+ cross the membrane through independent
pathways that open in response to a change
in membrane potential.
As testimony to their pioneering work, the
fundamental mechanisms described by
Hodgkin, Huxley and Katz remain applicable
to all excitable cells today. Indeed, the
predictions they made about the molecular
mechanisms that might underlie the changes
in membrane permeability showed remarkable
foresight. The molecular basis of the action
potential lies in the presence of proteins
called ion channels that form the permeation
pathways across the neuronal membrane.
Although the first electrophysiological
recordings from individual ion channels were
not made until the mid 1970s,2 Hodgkin and
Huxley predicted many of the properties now
known to be key components of their
function: ion selectivity, the electrical basis
of voltage-sensitivity and, importantly, a
mechanism for quickly closing down the
permeability pathways to ensure that the
action potential only moves along the axon in
one direction.

1. Action Potential NEHA AGARWAL 155066 B.SC. HONS DEI , AGRA

2. How Neurons Communicate Neurons communicate by means of an electrical signal called the Action Potential Action Potentials are based on movements of ions between the outside and inside of the axon When an Action Potential occurs, a molecular message is sent to neighboring neurons Action Potential is an All or Nothing Process (like a gun firing)

3. HOW THIS POTENTIAL IS GENERATED

4. To understand action potential, it is important to understand how the potential is maintained across the membrane

5. Na+ Na+ Na+ Na+ Na+ Na+ Na+ =sodium ions Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- = chloride ion Cl- Cl- Cl- Cl- K+ K+ K+ K+ K+ 2 K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ = potassium ions K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ 3 Na+ A- = organic A- A- A- A- A- A- A- A- E.C.F. I.C.F. Potassium pump Sodium pump Na/k pump Na+ POLARISATION

6. MEMBRANE (Resting) POTENTIAL Potential across membrane is called as membrane potential. Inside cell : conc. Of potassium ions and organic compounds is more than outside the cell ( negatively charged) Outside cell : concentration of chloride ions and sodium ions is more than inside the cell (positively charged) Sodium open/leaky chann els : flow of Na+ occurs in and out of cell Potassium open/ leaky channels : flow of K+ occurs in and out of cell Sodium-potassium pump : voltage gated channel; allow the efflux of 3 Na+ ions for influx every 2 K+ ions ; regulated by potential change across the membrane

7. All the above channels and pump maintains the resting potential (electro-chemical gradient) across the membrane i.e. -70 mV

8. Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ A- A- A- A- A- A- A- A- E.C.F. I.C.F. K+ voltage gated channels Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ DEPOLARISATION Na+ voltage gated channels

9. DEPOLARISATION As potential strike -55 mV (threshold potential) , Na+ voltage gated channels open , and allow the influx of Na+ ions into the cell. Due to influx of sodium ions, the potential across the membrane increases . More increase i n potential, more influx of ions This leads to change in charge across membrane. Inside_ +vely charged Outside_ -vely charged As this potential reaches +40 mV(overshoot), the , Na+ voltage gated channels closes, and the , K + voltage gated channels opens

10. REPOLARISATION As this potential reaches +40 mV, the , Na+ voltage gated channels closes, and the , K+ voltage gated channels opens. This leads to repolarisation This leads to efflux of potassium ions Thus the potential across the membrane decrease Inside_ -vely charged Outside_ +vely charged As the potential reaches -70mV, the potassium voltage-gated channels closes. However, due to gradual closing of channel, the is some amount of leaked ions, due to which the potential decreases below -70mV. This leads to HYPERPOLARISATION

11. Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ A- A- A- A- A- A- A- A- E.C.F. I.C.F. Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ REPOLARISATION K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

12. HYPERPOLARISATION AND REFRACTORY PERIOD Due to gradual closing of channel, the is some amount of leaked ions, due to which the potential decreases below -70mV. This leads to HYPERPOLARISATION the refractory period and the axon cannot fire again until it returns to resting potential (negative polarized state). Thus, the membrane undergoes the refractory period. In the refractory period ,the axon cannot fire again until it returns to resting potential (negative polarized state). It lasts for 3-5msec As the resting potential is restored via open channels and Na+/K+ pump, new action potential is fired.

13. Each spike is followed by a refractory period. An absolute refractory period - it is impossible to evoke another action potential – during spike and right after it (N a channels are open and after that inactivated) A relative refractory period - a stronger than usual stimulus is required to evoke an action potential ( hyperpolarization ; part of Na channels recovered)

14. All-or-None Principle Throughout depolarisation, the Na+ continues to rush inside until the action potential reaches its peak and the sodium gates close . If the potential cross -55mV , then the action potential will reach to its fate, via repolarisation and hyperpolarisation. If the depolarisation is not great enough to reach threshold , then an action potential and hence an impulse are not produced. This is called the All-or-None Principle.

15. Action Potential Within a Neuron

16. - without the depression (an energ y comes from the cell ) along nerve or muscle fibers - a wave (a spot) of ele ctrical negativity on the surface ( electrical po s itivity on the internal site of membrane ) due to openning and closing of voltage gated ion channels Propagation of action potential – local currents refractoriness

17. Threshold is reached +Na ions enter beginning of axon this triggers the next Na gates to open. As they open & allow in Na+, previous gates begin pumping the Na+ out. Before the action potential has reached the end, the beginning of the axon is back at resting potential & ready for another firing.

18. Graded potentials